Identifying the Genetic Predictors of Severe Acne Vulgaris and the Outcome of Oral Isotretinoin Treatment

Completed

• Conditions: Acne Vulgaris; Isotretinoin

• Registration Number: NCT01727440
• Lead Sponsor: Duke University

Brief Summary

The goal of this study is to enroll 250 participants that have joined the MURDOCK Study Horizon 1.5 (Duke IRB Pro00011196) with a current or prior diagnosis of severe acne AND current or prior treatment with oral isotretinoin. All 250 participants will answer a 5-page questionnaire designed to collect information on the diagnosis of severe acne and response to oral isotretinoin treatment. The aim is to identify genetic predictors of severe acne vulgaris and the outcome of oral isotretinoin treatment.

Detailed Description

Acne vulgaris is an under-studied common genetic disease with tremendous economic consequences. Acne vulgaris is one of the most common skin conditions treated by doctors. It affects 40-50 million people in the USA, with prevalence as high as 85% (recent study from Iran was 93%) in teenagers; 18% of woman have late onset (\>25yr) acne vulgaris. Severe acne has a life-long psychosocial impact due to the significant scarring. Severe acne can also be associated with severe systemic inflammatory disease with fever, sterile osteomyelitis, inflammatory arthritis and other signs of systemic inflammatory responses. Some of these syndromes in Mendelian form (e.g. PAPA syndrome) have known genetic defects. Finally, while the data are inconclusive, there have been many suggestions that diet can exacerbate acne in some patients. The standard of care treatment for severe acne is systemic retinoid therapy, which, is usually, but not always effective. Unfortunately, systemic retinoid treatment is associated with significant toxicity, including common cutaneous adverse effects (dry lips, eyes, skin fragility), less common laboratory abnormalities such as elevated blood lipids, liver function abnormalities, and severe predictable teratogenicity. In addition, systemic therapy with retinoids has been associated with systemic diseases such as clinical depression, suicide, and inflammatory bowel disease, however the mechanisms and significance of these associations has not been determined. Given the frequency and severity of severe acne, the predictable severe toxicity of systemic retinoid therapy, and the already demonstrated genetic associations found in Mendelian forms of severe acne, it seems likely that significant genetic risk factors may be identified in patients with severe acne which would promote new and safer therapy, including dietary adjustment.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2012-10-24
• Study First Submitted QC: 2012-11-12
• Study First Posted: 2012-11-16
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2017-01
• Last Update Submitted: 2017-08-23
• Last Update Posted: 2017-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 123

Inclusion Criteria

• Diagnosed with severe acne while age > 12 and < 18, and
• Completed at least one course of oral isotretinoin treatment; OR started treatment but discontinued prior to completion due to adverse side effects (with the exception of dry skin - see "exclusion criteria"); OR are currently undergoing and plan to complete treatment

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Exclusion Criteria

• Patients who are not willing to participate in this study
• Patients who experienced inflammatory bowel disease (IBD) prior to oral isotretinoin treatment
• Patients who did not complete the oral isotretinoin treatment because of pregnancy, dry skin, or reasons other than adverse side effects listed above
• Patients who are not willing to or cannot provide a blood sample for Murdock Study

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Therapeutic response to isotretinoin	10 months	All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).

Secondary Outcome Measures

Name	Time	Method
Adverse reaccion to isotretinoin	10 months	All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).

Trial Locations

Locations (6)

Harrisburg Sleep Center; 🇺🇸 Harrisburg, North Carolina, United States

Kannapolis Internal Medicine; 🇺🇸 Kannapolis, North Carolina, United States

Ada Jenkins Center; 🇺🇸 Davidson, North Carolina, United States

Carolinas Medical Center Northeast Medical Arts Building; 🇺🇸 Concord, North Carolina, United States

Dermatology Group of the Carolinas; 🇺🇸 Concord, North Carolina, United States

Lake Norman Community Health Clinic; 🇺🇸 Huntersville, North Carolina, United States